1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling

Sumit Sethi, Mariana Pedrini, Lucas B. Rizzo, Maiara Zeni-Graiff, Caroline Dal Mas, Ana Cláudia Cassinelli, Mariane N. Noto, Elson Asevedo, Quirino Cordeiro, João G. M. Pontes, Antonio J. M. Brasil, Acioly Lacerda, Mirian A. F. Hayashi, Ronei Poppi, Ljubica Tasic, Elisa Brietzke

The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Metabolomic profiling, employing (1)H-NMR, (1)H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.